Tag: CLL

FDA Approves Ofatumumab for Additional CLL Patients

The Backstory

On January 19, 2016, the FDA approved the use of ofatumumab to treat patients with recurrent or progressive chronic lymphocytic leukemia (CLL) who are in complete or partial response following at least two prior treatment therapies.

This is the third time ofatumumab has received FDA approval for the treatment of patients with CLL. Ofatumumab was initially approved in 2009 for the treatment of patients with CLL who are refractory to fludarabine and alemtuzumab, and subsequently approved in April 2014 for use in combination with chlorambucil for previously untreated patients with CLL.

This approval is for the use of ofatumumab as a maintenance therapy. A maintenance therapy is an additional therapy that is administered to a patient after completion of an initial therapy in order to prolong the response achieved.

What is ofatumumab?

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecules found on the surface of CLL cells and B-cell lymphocytes. CD20 molecules are found in over 90% of B-cell lymphomas. Ofatumumab is an immunotherapy that works by attaching itself to the CD20 molecule found on the surface of B-cells and directs the immune system to kill the cancerous B-cells.

Why was ofatumumab granted FDA approval?

Ofatumumab received this FDA approval based on the results from the PROLONG trial. In this phase III study, the use of ofatumumab as maintenance therapy was evaluated against no further treatment of patients who were in a complete or partial response after second or third line CLL treatment. The trial demonstrated an improvement in progression free survival for patients receiving ofatumumab maintenance of 29.4 months compared with 15.2 months for those on observation.

Were there any side effects?

Common side effects included infusion reactions, neutropenia, and upper respiratory tract infection. There were no unexpected, or new side effects observed for the patients receiving ofatumumab maintenance. The most common side effects seen were those previously described with ofatumumab infusions, including infusion reactions, low neutrophil counts, and infections.

How can you access ofatumumab now?

While all available trials for people with CLL at WCM have recently closed, our understanding of how best to use ofatumumab continues to increase. You can look to this space for further updates on CLL trials examining the use of ofatumumab.

A full list of trials open at WCM for patients with CLL is available on our Joint Clinical Trials website.

FDA Expedites Review of New CLL Treatment

The Backstory

DRFurman_5284In May 2015, the Federal Drug Administration (FDA) granted venetoclax a breakthrough therapy designation for treating patients with relapsed or refractory chronic lymphocytic leukemia (CLL) with a specific genetic alteration – the 17p deletion. A second FDA breakthrough therapy designation was granted to venetoclax earlier this month for use in combination with rituximab (Rituxan) to treat patients with relapsed/refractory CLL. Last week, the FDA announced that they are granting “Priority Review” to venetoclax. This means that the treatment has been shown to be so effective compared to standard treatment options that the FDA is committed to allocating significant resources to further evaluate it. The label of Priority Review can be of great help in getting new, promising treatment options to more people as quickly as possible.

What is venetoclax?

Venetoclax (also known as ABT-199) is an oral inhibitor of the bcl-2 (B-cell lymphoma 2) protein. BCL-2 protein plays a critical role in preventing cells from undergoing apoptosis (cell death), including CLL cells.

Why did the FDA decide to grant Priority Review to venetoclax?

This Priority Review status is based upon results presented by investigators at the 2015 annual meeting of the American Society of Hematology (ASH) that took place in early December.

In this study, they found that of the 107 patients treated, 85 patients (79.4%) responded to treatment with venetoclax.

Of these patients who responded, eight patients (7.5%) experienced a complete response, meaning that no detectable levels of cancer remained. Three patients (2.8%) experienced nodular partial response (nPR), while 74 patients (69.2%) experienced partial response. Unlike a complete response a nPR includes some persistent remaining modules of lymphocytes. In the past it was difficult to differentiate these CLL cells from normal cells. However, we now know that patients with nPR do better than patients with partial responses, but not as well as complete responses.

Were there any side effects?

The side effect of primary concern based upon earlier studies was tumor lysis syndrome, which occurs when the CLL cells breakdown too rapidly and release too many of their breakdown products at one time, potentially causing kidney failure and death. Researchers sought to implement strategies to minimize the risk of tumor lysis.  Other side effects were comparable or less prevalent than those experienced by people who received current standard chemotherapy treatment for CLL.

How can you access venetoclax now?

At Weill Cornell Medicine, we have a clinical trial with venetoclax already underway for relapsed/refractory CLL patients who have previously been treated with an inhibitor of the BCR signaling pathway, including idelalisib or ibrutinib. If you are interested in enrolling in or learning more about this clinical trial, please contact Amelyn Rodriguez RN, by email amr2017@med.cornell.edu or phone (212) 746-1362.

Dr. Richard Furman Joins Panel Discussion on CLL Prognostic Factors and the Impact on New Therapies

In this video from OncLive, CLL Program Director, Dr. Richard Furman joins a panel of chronic lymphocytic leukemia (CLL) experts to discuss the use of a new prognostic index for patients with CLL and its impact on new therapies.

A full transcript of Dr. Furman’s comments are below:

I can’t agree enough with Dr. Kipps in the importance of being able to use in clinical practice helpful measures for our patients. And no matter what new prognostic factors we develop, and of course, CLL doesn’t really need any more prognostic factors, it’s really going to be dependent upon those classic criteria from the original IWCLL or NCI working groups, based upon progression of disease, Rai stage, and all those factors that are just clinically apparent that are going to determine when you’re going to initiate therapy.

And fortunately, with these new agents, the novel agents, the prognostic markers really don’t become relevant in terms of response to treatment. Where I really think the majority of effort needs to be in this day and age is going to be identifying those patients who are unlikely to be basically maintained on a BCR antagonist long-term.

There are some patients with 17p deletion or some other genetic abnormalities that might have or are likely to have progression on a BCR antagonist. And those are the prognostic markers that we need to identify because they’re the ones that are going to tell us that ibrutinib by itself is not going to be long-term the best option for this patient.

And I think likewise looking at the gene family 4-39 or notch 1 mutations, things that predict for Richter’s Transformation, which is often a mode of escape from the BCR antagonists, really become increasingly important. Because those are the things that really may indicate to us that we have to change our treatment strategy.